PURPOSE: The purpose of this study is to identify a safe dose(s) if rhIGF-1 that, when administered in combination with glyburide, or as sole therapy, will improve glycemic control compared with administration of glyburide alone in subjects with type 2 diabetes mellitus. METHODS: This is a phase II, double-blind, randomized, placebo-controlled multicenter study which will evaluate the safety and pharmacokinetic and pharmacodynamic effects of rhIGF-1. Approximately 200 patients (a total for all sites) with type II diabetes will be evaluated in this trial. RhIGF-1 or rhIGF-1 placebo (20ug/kg BID or 40 ug/kg BID) will be administered subcutaneously in addition to oral glyburide or glyburide placebo. The study consists of a two week screening period, a four week pretreatment period, a twelve week treatment period, and a two week followup period. At our site, patients were admitted to the GCRC for pharmacokinetic evaluation of the study medications at the beginning and end of the treatment period.